Gene therapy has drawn lots of attention in the studies for cancer treatment. The efficiency of transduction and expression of therapeutic genes in tumor cells are critical for gene therapy methods. Various approaches have been developed for improving the efficiencies of gene transduction and expression in tumor cells. Various viruses have been studied and tested for their potential to be used as vectors for carrying genes of interests to tumor cells. However, the safety and selectivity of a viral vector for tumor cells are major issues of concern when selecting viral vectors as candidates for gene therapy.
Vaccinia virus is closely related to the virus that causes smallpox and has been used as a live vaccine in the smallpox eradication program. It has recently become a subject of study as a vector for carrying and delivering genes of interests to a subject under treatment in gene therapy.
Vaccinia virus contains two copies of the vaccinia growth factor (VGF) genes which are located in the inverted terminal repetition (ITR) of the vaccinia virus genome. The VGF protein is a highly glycosylated 77-residue epidermal growth factor (EGF)-like polypeptide. The VGF protein is expressed and secreted early in viral infection and acts as a mitogen to prime surrounding cells for vaccinia infection and has been shown to play a critical role in vaccinia virus infection (Buller et al. J. Virol. 62 (1988): 866-74).
Vaccinia virus also contains Serpin genes and Ankyrin genes. Serpin genes are a family of genes that encode serine protease inhibitors. Serpins are potentially involved in multiple biological functions such as regulation of coagulation, fibrinolysis, immune response, inflammation, tumor invasion and apoptosis (see Kummer et al. Methods 32 (2004): 141-9). Ankyrin genes encode a family of proteins that possess binding sites for different integral membrane proteins and play a critical role in biological process involving protein-protein interaction (see Li et al. Biochemistry 45 (2006): 15168-78).